Download MendeleyDiscovery of a new 2-aminobenzhydrol template for highly potent squalene synthase inhibitors
Ichikawa, M., Yokomizo, A., Itoh, M., Sugita, K., Usui, H., Shimizu, H., Suzuki, M., Terayama, K., Kanda, A.(2011) Bioorg Med Chem 19: 1930-1949
- PubMed: 21353782
- DOI: https://doi.org/10.1016/j.bmc.2011.01.065
- Primary Citation of Related Structures:
3ASX, 3Q2Z, 3Q30 - PubMed Abstract:
To obtain small and efficient squalene synthase inhibitors, a flexible 2-aminobenzhydrol open form structure was designed and showed potent inhibitory activity comparable to 4,1-benzoxazepin compounds. Further chemical modification led to the discovery of a novel template with a strong squalene synthase inhibitory activity, and its basic structure-activity relationship was revealed. The X-ray crystallographic data of compound 12 bound to the active site of squalene synthase provided an important insight into the binding mode of this alternative template that formed 11-membered ring conformations with an intramolecular hydrogen bond.
Organizational Affiliation:
Lead Discovery and Optimization Research Laboratories I, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. [email protected]
